The etiology for diabetes is known to be mostly owing to disturbances of insulin secretion in the pancreatic .beta.-cells. Consequently, elucidation of the molecular mechanism of insulin secretion is expected to play an important role in the clarification of causes for diabetes and the development of therapeutic agents against diabetes, but no detail has yet been made known on such molecular mechanism.
It has already been made clear that the ATP-sensitive potassium channel (K.sub.ATP) being present on the cellular membrane plays a leading role in the cellular functions such as secretions and muscular contraction by coupling the state of metabolism in the cells with the membrane potential.
The K.sub.ATP channel was first discovered in the cardiac muscle in 1983 Noma, A., Nature 305:147 (1983)! and was thereafter confirmed to be present in tissues such as the pancreatic .beta.-cell Cook, D. L. et al., Nature 311:271 (1984), Misler, S. et al., Proc. Natl. Acad. Sci. U.S.A. 83:7119 (1986)!, pituitary Bernardi, H. et al., Proc. Natl. Acad. Sci. U.S.A., 90:1340 (1993)!. skeletal muscle Spruce, A. E., et al., Nature, 316:736 (1985)! and brain.
In addition, it has been suggested that there exists the molecular heterogeneity of such K.sub.ATP channels Ashcroft, F. M., Annu. Rev. Neurosci. 11:97 (1988)!.
Particularly in the pancreatic .beta.-cells, ATP produced by the metabolism of glucose brings about calcium ion inflow from the calcium channel by closing the K.sub.ATP channel to cause depolarization, resulting in secretion of insulin. As is evident from this, the K.sub.ATP channel plays a leading role in regulating the secretion of insulin.
The K.sub.ATP channel belongs to a potassium channel family exhibiting electrophysiologically inward rectification, whereby the potassium channel family exhibiting inward rectification is classified into the four subfamilies, ROMK1, IRK1, GIRK1 and cK.sub.ATP -1, on the basis of the degree of amino acid sequence identity.
Nevertheless, there has not been clarified the molecular architecture for the K.sub.ATP channel in the pancreatic .beta.-cells. In addition, no information has been disclosed on the novel ATP-sensitive potassium channels (huK.sub.ATP -1 and ruK.sub.ATP -1) of the present invention for the detailed protein structure and the formation of complexes with other proteins, for example, the sulfonylurea binding protein.